Life-threatening Pneumonia Research Articles

SARS-CoV-2 pathogenesis.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating pandemic. Although most people infected with SARS-CoV-2 develop a mild to moderate disease with virus replication restricted mainly to the upper airways, some progress to having a life-threatening pneumonia. In this Review, we explore recent clinical and experimental advances regarding SARS-CoV-2 pathophysiology and discuss potential mechanisms behind SARS-CoV-2-associated acute respiratory distress syndrome (ARDS), specifically focusing on new insights obtained using novel technologies such as single-cell omics, organoid infection models and CRISPR screens. We describe how SARS-CoV-2 may infect the lower respiratory tract and cause alveolar damage as a result of dysfunctional immune responses. We discuss how this may lead to the induction of a 'leaky state' of both the epithelium and the endothelium, promoting inflammation and coagulation, while an influx of immune cells leads to overexuberant inflammatory responses and immunopathology. Finally, we highlight how these findings may aid the development of new therapeutic interventions against COVID-19.

Clinical and Epidemiological Characteristics of Stenotrophomonas maltophilia Associated Lower Respiratory Tract Infections in Qatar: A Retrospective Study.

BackgroundStenotrophomonas maltophilia is a rapidly emerging nosocomial pathogen with intrinsic or acquired resistance mechanisms to several antibiotic classes. It can cause life-threatening opportunistic pneumonia, particularly among hospitalized patients. Incidence of infections by S. maltophilia has been reported as 0.07-0.4% of hospital discharges, but its mortality is 20 -60%. This is the first study from Qatar indexing the clinical and epidemiological characteristics and antibiotic susceptibility of S. maltophilia.Materials and methodsThis retrospective descriptive epidemiological study was conducted in 6 tertiary care hospitals under Hamad Medical Corporation in Doha, Qatar, analyzing inpatient respiratory isolates of S. maltophilia during 2016-17. Out-patients, children below 14 years, and non-respiratory samples except blood cultures in patients with pneumonia were excluded. Clinical records were reviewed to identify possible risk factors. Infection and colonization were identified using the Centers for Disease Control and Prevention (CDC) algorithm for clinically defined pneumonia and statistically analyzed using the chi-square test and Pearson's correlation.ResultsS. maltophilia was isolated from 2.07% (317/15312) of all respiratory samples received in the microbiology lab during our study period. Three hundred seventeen patients studied had a mean age of 60 ± 20 years, and 68% were men. Most of the isolates were from sputum (179), followed by tracheal aspirate (82) and bronchoscopy (42). Fourteen blood culture samples from patients diagnosed with pneumonia were also included. 67% were hospitalized for more than two weeks, 39.1% were on mechanical ventilators, and 88% had received a broad-spectrum antibiotic before the event. 29.1% were deemed to have an infection and 70.9% colonization. Incidence of infection in those with Charlson’s Co-morbidity Index (CCI) ≥ 3 was 36.5% compared to 24.2% in those with CCI < 3 (Relative Risk (RR)=1.52; 95% CI: 1.04,2.18; p=0.01). Patients with recent chemotherapy, immunosuppressant, or steroid use had a significantly higher infection risk than those without (69.2% v/s 23.3% RR=2.96; 95% CI:2.2,3.9; p<0.005). The most common symptoms in patients with infection were fever (96%) and expectoration (61.9%). The most common radiological finding was lobar consolidation (71.6%). Mean CRP and procalcitonin were 106.5±15.5 mg/l and 12.3 ± 14 ng/ml. Overall mortality was 16.3%. Patients on mechanical ventilator with IBMP-10 score ≥ 2 had 22.8% mortality compared to 5.7% in those with score < 2 (RR=3.9;95%CI:0.9,16.6; p<0.015). As per The US Clinical and Laboratory Standards Institute (CSLI) breakpoint values, Trimethoprim-Sulfamethoxazole (TMP-SMX) showed the highest sensitivity (97.8%), followed by levofloxacin (71.6%). 0.3% of samples were pan-drug resistant.ConclusionsS. maltophilia is a frequent nosocomial colonizer, but it can cause nosocomial pneumonia in almost one-third of cases, specifically in immunocompromised and patients with CCI ≥ 3 with a high risk of mortality due to ventilator-associated pneumonia (VAP) in those with IBMP-10 ≥ 2. Prolonged hospital stay is a risk factor for colonization by S. maltophilia, while recent chemotherapy, immunosuppressant, or steroid use are risk factors for hospital-acquired pneumonia due to S. maltophilia. TMP-SMX and levofloxacin are the only reliable agents for monotherapy of respiratory infections due to S. maltophilia in Qatar.

Recent Approaches of Drugs and Vaccines Used in COVID 19: A Review

A novel SARS-CoV-2 coronavirus developed in December 2019, triggering a life-threatening pneumonia outbreak in China, and has since expanded worldwide, producing a pandemic. Because of the urgent need to control the disease and the dearth of specific and effective treatment options, FDA-approved medicines that have proven efficacy against comparable viruses are being used. In vitro, chloroquine, remdesivir, lopinavir/ritonavir or ribavirin are effective at inhibiting SARS-CoV-2. The preliminary findings of a variety of clinical trials utilising various chloroquine or hydroxychloroquine delivery procedures all indicate a positive outcome. They may not be effective in cases of consistently high viremia, and data on ivermectin (another antiparasitic medication) is currently unavailable. Intriguingly, azithromycin, a macrolide antibiotic, in conjunction with hydroxychloroquine may provide therapeutic benefits. Favipiravir, tocilizumab, and azithromycin types are among the other treatment options being investigated.

Pneumocystis Colonization in Dogs Is as in Humans.

Pneumocystis is an atypical fungus that resides in the pulmonary parenchyma of many mammals, including humans and dogs. Immunocompetent human hosts are usually asymptomatically colonised or show subtle clinical signs, but some immunocompromised people can develop florid life-threatening Pneumocystis pneumonia (PCP). Since much less is known concerning Pneumocystis in dogs, we posit the question: can Pneumocystis colonization be present in dogs with inflammatory airway or lung disease caused by other pathogens or disease processes? In this study, Pneumocystis DNA was detected in bronchoalveolar lavage fluid (BALF) of 22/255 dogs (9%) with respiratory distress and/or chronic cough. Although young dogs (<1 year-of-age) and pedigree breeds were more often Pneumocystis-qPCR positive than older dogs and crossbreds, adult dogs with other infectious conditions and/or a history of therapy-resistant pulmonary disease could also be qPCR-positive, including two patients with suppression of the immune system. Absence of pathognomonic clinical or radiographic signs render it impossible to convincingly discriminate between overt PCP versus other lung/airway disease processes colonised by P. canis. It is possible that colonisation with P. canis might play a certain role as a co-pathogen in some canine patients with lower respiratory disease.

Decode: COVID-19 Associated Mucormycosis

The coronavirus infection caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be related with a wide range of disease and ranging from mild to life-threatening pneumonia. Patients with COVID-19 have higher susceptibility to fungal coinfections. Mucormycosis is a rare and-threatening fungal infection. Mucormycosis is more common in immunocompromised individuals, and patients with uncontrolled diabetes. COVID-19 associated mucormycosis usually developed 10-14 days after hospitalization. A high number of suspicion diagnosis and aggressive management is required to improve outcomes of the therapy. Awareness of warning symptoms and signs play an important role for the identification of the mucormycosis.

Microbe Profile: Legionella pneumophila - a copycat eukaryote.

Legionella pneumophila is an environmental bacterium that parasitizes aquatic protozoa and uses the same processes to infect humans. The facultative intracellular pathogen causes a life-threatening pneumonia with possible systemic complications. The co-evolution with protozoa is reflected in an armoury of bacterial effectors, and many of these type IV-secreted proteins have likely been acquired by interdomain horizontal gene transfer (HGT) from hosts. The unique features of L. pneumophila are the largest bacterial effector repertoire known to date, subversion of virtually all eukaryotic signalling pathways and acquisition of eukaryotic enzyme activities used to manipulate the host cell to the pathogen's advantage.

Host Genetic Susceptibility and Impacts of Dietary Factors on Covid-19

COVID-19, a disease caused by SARS coronavirus 2 (SARS-CoV-2) has been a virus which is causing a global issue due to the fact that it resulted in a pandemic. The SARS coronavirus 2 binds with the angiotensin-converting enzyme 2 (ACE-2) receptors expressed in various human organs including the lungs. The SARC-CoV-2 causes respiratory disease ranging from mild to life-threatening pneumonia. Covid-19 is much feared due to its ultimate outcome such as multi-organ damage as a result of the production of a high level of pro-inflammatory cytokines referred to as “cytokine storm and resulting increased mortality and morbidity. Outcomes of the COVID 19 infection are associated with several factors that include demographic, environmental, behavioural, dietary, and genetic factors. In addition, male gender, ethnicity, older age, obesity, and several chronic diseases affect the severity of the disease. Genetic susceptibility and dietary factors involved with COVID – 19 infectivity are current areas that are widely researched and likely to play a major role. Through Genome Wide Association Studies (GWAS) and other studies done worldwide, scientists have discovered variants related to the susceptibility and severity of COVID-19. Among published reports, the involvement of ACE-2, TMPRSS2, 3p21.31 gene cluster, OAS1, OAS2 and OAS3, TYK2, DPP9, IFNAR2, CCR2 TMEM189–UBE2V1 genes, IFNL4, TLR7, LZTFL1, CCHCR1, CCNG1, ACSF3, FPR1, NKG2C/HLA-E, NLRP3, DNAH7 and CLUAP1, DES and SPEG, STXBP5, TOMM7, WSB1, PIEZO1, SCN5A, APOL1, PRKRA, GC, NADSYN1, VDR, and CYP2R1, PPCDC, VDR, DMGDH is summarized in this review. Similarly, this review concluded the role of nutrition in terms of the importance of a balanced diet and functional foods, micronutrients, probiotics, and how the omega 3/omega 6 ratio helps to prevent the severity of COVID-19.

The Role of Ionizing Radiation for Diagnosis and Treatment against COVID-19: Evidence and Considerations.

The Coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide with over 260 million people infected and more than 5 million deaths, numbers that are escalating on a daily basis. Frontline health workers and scientists diligently fight to alleviate life-threatening symptoms and control the spread of the disease. There is an urgent need for better triage of patients, especially in third world countries, in order to decrease the pressure induced on healthcare facilities. In the struggle to treat life-threatening COVID-19 pneumonia, scientists have debated the clinical use of ionizing radiation (IR). The historical literature dating back to the 1940s contains many reports of successful treatment of pneumonia with IR. In this work, we critically review the literature for the use of IR for both diagnostic and treatment purposes. We identify details including the computed tomography (CT) scanning considerations, the radiobiological basis of IR anti-inflammatory effects, the supportive evidence for low dose radiation therapy (LDRT), and the risks of radiation-induced cancer and cardiac disease associated with LDRT. In this paper, we address concerns regarding the effective management of COVID-19 patients and potential avenues that could provide empirical evidence for the fight against the disease.

Type I interferons and SARS-CoV-2: from cells to organisms.

Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type I IFNs and SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of type I IFNs, and SARS-CoV-2 proteins can inhibit various steps in type I IFN production and response. Exogenous type I IFNs inhibit viral growth in vitro. In various animal species infected in vivo, type I IFN deficiencies underlie higher viral loads and more severe disease than in control animals. The early administration of exogenous type I IFNs improves infection control. In humans, inborn errors of, and auto-antibodies against type I IFNs underlie life-threatening COVID-19 pneumonia. Overall, type I IFNs are essential for host defense against SARS-CoV-2 in individual cells and whole organisms.

The Legionella Lqs-LvbR Regulatory Network Controls Temperature-Dependent Growth Onset and Bacterial Cell Density.

Legionella species are facultative intracellular pathogens that cause a life-threatening pneumonia termed Legionnaires' disease. Legionella pneumophila employs the Lqs-LvbR (Legionella quorum sensing-Legionella virulence and biofilm regulator) network to regulate virulence and motility, but its role for growth in media is ill-defined. Here, we report that compared to the L. pneumophila reference strain JR32, a ΔlqsR mutant showed a reduced lag phase at 30°C and reached a higher cell density at 45°C, while the ΔlqsA, ΔlqsS, and ΔlqsT mutants showed a longer lag phase and reached a lower cell density. A ΔlvbR mutant resumed growth like the parental strain at 30°C but exhibited a substantially reduced cell density at 45°C. Thus, LvbR is an important cell density regulator at elevated temperatures. Environmental and clinical L. pneumophila strains grew in N-(2-acetamido)-2-aminoethanesulfonic acid (ACES)-buffered yeast extract (AYE) medium after distinct lag phases with similar rates at 30°C, reached different cell densities at the optimal growth temperature of 40°C, and no longer grew at 50°C. Legionella longbeachae reached a rather low cell density at 40°C and did not grow at and beyond 45°C. Genes encoding components of the Lqs-LvbR network were present in the genomes of the environmental and clinical L. pneumophila isolates, and upon growth at 30°C or 45°C, the PlqsR, PlqsA, PlqsS, and PlvbR promoters from strain JR32 were expressed in these strains with distinct patterns. Taken together, our results indicate that the Lqs-LvbR network governs the temperature-dependent growth onset and cell density of the L. pneumophila reference strain JR32 and possibly also of environmental and clinical L. pneumophila isolates. IMPORTANCE Environmental bacteria of the genus Legionella are the causative agents of the severe pneumonia Legionnaires' disease, the incidence of which is on the rise worldwide. Legionella pneumophila and Legionella longbeachae are the clinically most relevant species. The opportunistic pathogens are inhaled through contaminated aerosols and replicate in human lung macrophages with a mechanism similar to that in their natural hosts, free-living amoebae. Given their prevalence in natural and technical water systems, an efficient control of Legionella spp. by physical, chemical, or biological means will reduce the incidence of Legionnaires' disease. Here, we show that the Legionella quorum sensing (Lqs) system and the pleiotropic transcription factor LvbR govern the temperature-dependent growth onset and cell density of bacterial cultures. Hence, the growth of L. pneumophila in water systems is determined not only by the temperature and nutrient availability but also by quorum sensing, i.e., density- and signaling molecule-dependent gene regulation.

Meta-Analysis the Effectiveness of Ivermectin Use on the Length of Stay in Inpatients of COVID-19

Background: COVID-19 is a common problem in global health. COVID-19 is a disease that infects the respiratory tract caused by the Coronavirus virus. Symptoms range from mild to severe and life-threatening pneumonia can occur. At the beginning of the PSBB, information circulated that Ivemectin could treat COVID-19 infections. Ivermectin is an antiparasitic drug that can be used as prophylaxis and therapy for coronavirus disease 2019. Ivermectin is an alternative therapy for COVID-19 because there is a previous drug, chloroquine, which can be used to treat COVID-19. This study aims to estimate the effectiveness of Ivermectin on the duration of hospitalization of patients with COVID-19 based on the results of previous similar studies. Subjects and Method : This study is a meta-analysis with the following PICO, population: COVID-19 patients. Intervention: ivermectin. Comparison: standard therapy. Outcome: shorter duration of hospital stay. Meta-analyses and systematic studies using the PubMed, Scopus, Scholar, Springlink, Cochrane, Clinical Key, and Science Direct databases. Keywords using Ivermectin AND RCT AND COVID-19 AND “Coronavirus Disease” AND “NCOV disease” AND “COVID-19 treatment”. The article under study is a full-text article with a randomized controlled clinical trial (RCT) study design. Articles were collected using PRISMA diagrams and analyzed using Review Manager 5.3. Results A total of 9 Randomized Control Trial (RCT) studies from Europe, America, Asia and Africa were selected for systematic review and meta-analysis. COVID-19 patients receiving Ivermectin therapy decreased the duration of hospital stay by 1.52 units compared to standard therapy and this result was statistically significant (SMD= -1.52; 95% CI= -2.34 to -0.70; p= 0.003). Conclusion: Ivermectin can reduce the duration of hospital stay for COVID-19 patients. Keywords: COVID-19, ivermectin, duration hospital stay Correspondence: Masromi Hendria Wijayanto. Masters Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta 57126, Jawa Tengah. Email: masromi­hendria@gmail.com. Mobile: 0895402471549. Indonesian Journal of Medicine (2022), 07(02): 200-208 https://doi.org/10.26911/theijmed.2022.07.02.08

Potential Association of Legionnaires' Disease with Hot Spring Water, Hot Springs National Park and Hot Springs, Arkansas, USA, 2018-2019.

Legionella pneumophila is the cause of Legionnaires’ disease, a life-threatening pneumonia that occurs after inhalation of aerosolized water containing the bacteria. Legionella growth occurs in stagnant, warm-to-hot water (77°F–113°F) that is inadequately disinfected. Piped hot spring water in Hot Springs National Park, Arkansas, USA, has naturally high temperatures (>135°F) that prevent Legionella growth, and Legionnaires’ disease has not previously been associated with the park or other hot springs in the United States. During 2018–2019, Legionnaires’ disease occurred in 5 persons after they visited the park; 3 of these persons were potentially exposed in spa facilities that used untreated hot spring water. Environmental testing revealed Legionella bacteria in piped spring water, including 134°F stagnant pipe water. These findings underscore the importance of water management programs to reduce Legionella growth in plumbing through control activities such as maintaining hot water temperatures, reducing stored water age, and ensuring adequate water flow.

Cell death induction in Aspergillus fumigatus: accentuating drug toxicity through inhibition of the unfolded protein response (UPR).

One of the most potent opportunistic fungal pathogens of humans is Aspergillus fumigatus, an environmental mold that causes a life-threatening pneumonia with a high rate of morbidity and mortality. Despite advances in therapy, issues of drug toxicity and antifungal resistance remain an obstacle to effective therapy. This underscores the need for more information on fungal pathways that could be pharmacologically manipulated to either reduce the viability of the fungus during infection, or to unleash the fungicidal potential of current antifungal drugs. In this review, we summarize the emerging evidence that the ability of A. fumigatus to sustain viability during stress relies heavily on an adaptive signaling pathway known as the unfolded protein response (UPR), thereby exposing a vulnerability in this fungus that has strong potential for future therapeutic intervention.

Surgical Interventions as a Treatment Option for Severe Dysphagia with Intractable Aspiration: Concept, Indications, and Efficacy

The incidence of dysphagia is increasing, particularly among the elderly according to varied of causes. Patients with severe dysphagia are unable to take food orally and are at risk for life-threatening aspiration pneumonia. Treatments for swallowing disorders focus on restoring oral food intake and preventing recurrent aspiration pneumonia. Therefore, swallowing rehabilitation and food texture modifications are essential. However, in cases with severe or progressive dysphagia, these conservative treatments may not restore oral feeding and prevent intractable aspiration pneumonia. In these cases, surgical interventions has recently been attracted as an alternative treatment option. In this article, we present its concept, indications, and efficacy. Surgeries to restore swallowing function address impaired pharyngolaryngeal motor function during the pharyngeal swallowing stage while preserving laryngeal functions. These procedures include laryngeal elevation, cricopharyngeal myotomy, and vocal cord medialization. Meanwhile, aspiration prevention surgeries reduce the risk of aspiration pneumonia by separating the lower respiratory tract from the pharynx and larynx. These procedures include total laryngectomy, laryngotracheal separation, and glottal closure; although they do not spare laryngeal functions, they prevent aspiration pneumonia completely, improve quality of life, and reduce the burden on caregivers. Clinicians should be aware of surgical interventions as a possible treatment option for intractable dysphagia. Establishment and popularization of the surgical indications are the future issues.

Study of mucormycosis in COVID-19 patients in a tertiary care center, Raichur Institute of Medical Sciences, Raichur.

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome (SARS-CoV-2), has become an emergency global public health issue. Disease pattern of COVID-19 ranges from mild to life-threatening pneumonia with associated bacterial and fungal coinfections. Due to associated comorbidities (e.g., diabetes mellitus and chronic obstructive pulmonary disease) and immunocompromised conditions (e.g., corticosteroid therapy), these patients are prone to develop severe opportunistic infections. The aim of this study was to investigate the incidence of fungal coinfection of hospitalized patients with COVID-19 infection (SARS-CoV-2) in RIMS, Raichur. Our study included 94 patients with invasive fungal infection who presented with either COVID-19 infection or had recovered from COVID-19 infection. Tissue samples from suspected sites were received in formalin for histopathological examination, and these were stained stains with hematoxylin and eosin and with periodic acid-Schiff/Gomori's methenamine silver wherever required. A total of 94 biopsies were received with clinical suspicion of mucormycosis. Out of these, 52 (55.3%) were positive for mucormycosis and 42 (44.7%) were negative. Out of 52 positive cases, 46 (88.4%) were males and 6 (11.6%) were females. The highest number of cases was seen in age group of 51-60 years (26.92%). Out of the 52 positive cases, KOH mount was positive for fungal elements in 8 cases and negative for fungal elements in 29 cases. Uncontrolled diabetes and overzealous use of steroids are two of the main factors aggravating the incidence of mucormycosis in COVID-19 patients. Early surgical intervention, histopathological confirmation and rapid and judicious intravenous antifungal treatment should be initiated for better patient outcomes.

Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice.

ABSTRACTMycoplasma pneumoniae (Mp) residing extracellularly in the respiratory tract is the primary cause of bacterial community-acquired pneumonia in humans. However, the detailed pathological mechanism of Mp infection, especially inflammation in the lung, remains unclear. This study examined the role of the neutrophils in the inflammation of Mp-induced pneumonia in mice and the mechanism of neutrophil infiltration into the lungs in the Mp-induced pneumonia. We observed massive infiltration of neutrophils in the bronchoalveolar lavage fluid (BALF) and lung injury after the Mp challenge. The neutrophils were shown to contribute to lung injury in Mp pneumonia but were not involved in eliminating Mp, suggesting that neutrophils are detrimental to the host in Mp pneumonia. Mp also induced the production of inflammatory cytokines and chemokines in the BALF in a toll-like receptor 2 (TLR2)-dependent manner. Particularly, both interleukin (IL)-1α and IL-12 p40 played a crucial role in neutrophil infiltration into the BALF in a coordinated manner. Both IL-1α and IL-12 p40 were released from the alveolar macrophages depending on the TLR2 and reactive oxygen species. In addition, the community-acquired respiratory distress syndrome (CARDS) toxin from Mp were found to induce neutrophil infiltration into BALF in a TLR2-independent and IL-1α-dependent manner. Collectively, the TLR2-dependent production of both IL-1α and IL-12 p40, and CARDS toxin have been elucidated to play an important role in neutrophil infiltration into the lungs subsequently leading to the lung injury upon Mp infection in mice. These data will aid in the development of therapeutics and vaccines for Mp pneumonia.IMPORTANCE Although Mp-induced pneumonia is usually a self-limiting disease, refractory life-threatening pneumonia is often induced. In addition, the development of alternative therapeutic strategies for Mp is expected because of the emergence of antibiotic-resistant Mp. However, the lack of knowledge regarding the pathogenesis of Mp-induced pneumonia, especially inflammation upon the Mp infection, makes it tedious to design novel therapeutics and vaccines. For example, although neutrophil infiltration is widely recognized as one of the characteristics of Mp-induced pneumonia, the precise role of neutrophils in the aggravation of Mp pneumonia remains unclear. This study showed that the infiltration of neutrophils in the lungs is detrimental to the host in Mp-induced pneumonia in mice. Furthermore, the TLR2-dependent IL-1α and IL-12 p40 production, and CARDS toxin play important roles in neutrophil infiltration into the lung, following lung injury. Our findings apply to the rational design of novel therapeutics and vaccines against Mp.

IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19.

IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19.

Identifying Mucormycosis Severity in Indian COVID-19 Patients: A Nano-Based Diagnosis and the Necessity for Critical Therapeutic Intervention.

The COVID-19 infection caused by the new SARS-CoV-2 virus has been linked to a broad spectrum of symptoms, from a mild cough to life-threatening pneumonia. As we learn more about this unusual COVID-19 epidemic, new issues are emerging and being reported daily. Mucormycosis, also known as zygomycosis or phycomycosis, causes severe fungal illness to individuals with a weakened immune system. It is a devastating fungal infection, and the most frequent kind is the rhino cerebral type. As a devastating second wave of COVID-19 sweeps India, doctors report several instances involving a strange illness—sometimes known as the “black fungus”—among returning and recovered COVID-19 patients. This paper analyzes the existing statistical data to address the severity of prevalence and further notes the nano-based diagnostic parameters, clinical presentations, its connection with other conditions like diabetes, hypertension, and GI disorders, and the importance of anti-fungal therapy in treating the same. Anti-fungal therapies, as well as surgical interventions, are currently used for the treatment of the disease. Proper and timely diagnosis is necessary, along with the reduction in the spread of COVID-19. From the review, it was found that timely pharmacologic interventions and early diagnosis by using a nano-based diagnostic kit can help control the disease. Additionally, this paper provides novel information about the nanotechnology approaches such as fungal detection biosensors, nucleic acids-based testing, point-of-care tests, and galactomannans detection, in the diagnosis of mucormycosis, and thereby reinforces the need for further research on the topic.

Innate immune responses at the asymptomatic stage of influenza A viral infections of Streptococcus pneumoniae colonized and non-colonized mice

Seasonal Influenza A virus (IAV) infections can promote dissemination of upper respiratory tract commensals such as Streptococcus pneumoniae to the lower respiratory tract resulting in severe life-threatening pneumonia. Here, we aimed to compare innate immune responses in the lungs of healthy colonized and non-colonized mice after IAV challenge at the initial asymptomatic stage of infection. Responses during a severe bacterial pneumonia were profiled for comparison. Cytokine and innate immune cell imprints of the lungs were analyzed. Irrespective of the colonization status, mild H1N1 IAV infection was characterized by a bi-phasic disease progression resulting in full recovery of the animals. Already at the asymptomatic stage of viral infection, the pro-inflammatory cytokine response was as high as in pneumococcal pneumonia. Flow cytometry analyses revealed an early influx of inflammatory monocytes into the lungs. Neutrophil influx was mostly limited to bacterial infections. The majority of cells, except monocytes, displayed an activated phenotype characterized by elevated CCR2 and MHCII expression. In conclusion, we show that IAV challenge of colonized healthy mice does not automatically result in severe co-infection. However, a general local inflammatory response was noted at the asymptomatic stage of infection irrespective of the infection type.

The Polar Legionella Icm/Dot T4SS Establishes Distinct Contact Sites with the Pathogen Vacuole Membrane.

ABSTRACTLegionella pneumophila, the causative agent of Legionnaires’ disease, is a facultative intracellular pathogen that survives inside phagocytic host cells by establishing a protected replication niche, termed the “Legionella-containing vacuole” (LCV). To form an LCV and subvert pivotal host pathways, L. pneumophila employs a type IV secretion system (T4SS), which translocates more than 300 different effector proteins into the host cell. The L. pneumophila T4SS complex has been shown to span the bacterial cell envelope at the bacterial poles. However, the interactions between the T4SS and the LCV membrane are not understood. Using cryo-focused ion beam milling, cryo-electron tomography, and confocal laser scanning fluorescence microscopy, we show that up to half of the intravacuolar L. pneumophila bacteria tether their cell pole to the LCV membrane. Tethering coincides with the presence and function of T4SSs and likely promotes the establishment of distinct contact sites between T4SSs and the LCV membrane. Contact sites are characterized by indentations in the limiting LCV membrane and localize juxtaposed to T4SS machineries. The data are in agreement with the notion that effector translocation occurs by close membrane contact rather than by an extended pilus. Our findings provide novel insights into the interactions of the L. pneumophila T4SS with the LCV membrane in situ.